Emergency department pharmacists shared their tips of the trade during the ED Pearls session at the recent American Society of Health-System Pharmacists Midyear Clinical Meeting. They offered advice on treating alcohol withdrawal, anticholinergic toxicity, pain during dermal procedures and more.

Topical Options for Analgesia In ED Depend on Procedure

There are various indications for topical analgesia in the emergency department (ED), and pharmacists should be aware of the available products and the clinical situations for which each product is best suited, said critical care pharmacist Courtney B. McKinney, PharmD, BCPS, in her ED pearl presentation.

The multiple uses of topical analgesic products in the ED—including venipuncture, laceration or abrasion debridement, first-degree burns, etc—as well as the different patient populations being treated, have different analgesic requirements. “The product you choose depends on the clinical scenario,” and the procedure being performed, said Dr. McKinney, from Intermountain Medical Center, in Salt Lake City.

There are many available formulations, such as aerosols, creams, gels, ointments and solutions for injection, as well as compounded products. The key considerations in product selection include whether the skin is broken or intact, the surface area of the involved skin, what procedure is being done, and how long the procedure takes. Three commonly used products are lidocaine 2.5%, prilocaine 2.5% oil-in-water eutectic mixture (EMLA); lidocaine 4% liposomal cream (LMX, Ferndale); and lidocaine 4%, epinephrine 0.05%, tetracaine 0.5% (LET) solution or gel.

The dose of EMLA is 1 to 2 g/cm2 with a maximum of 5 mg/kg of lidocaine. It can be applied only to intact skin and requires an occlusive dressing. The onset of action is 45 to 60 minutes and the effect lasts two hours after removal of the dressing. Dr. McKinney noted that the benefits of EMLA are that “it is long-lasting, can be used on mucous membranes and has been used in neonates.” However, because of its relatively long onset, she said that it is best used in “planned dermal procedures.”

Lidocaine 4% liposomal cream is another commonly used topical anesthetic. The dose is also 1 to 2 g/cm2 with a maximum of 5 mg/kg of lidocaine. It also should be used on intact skin only and the skin should not be washed before application “because the oils actually help it to get absorbed down into the dermal layers,” noted Dr. McKinney. Lidocaine 4% liposomal cream does not require an occlusive dressing, but she said it is recommended. Its onset is 30 minutes and the duration is 60 minutes. Dr. McKinney noted that it is good for minor burns or planned/nonemergent dermal procedures, but there are no safety data on this product in children younger than age 2.

LET solution or gel is a sterile compounded product that also has a role in certain ED pain scenarios, noted Dr. McKinney.The dose she recommended is 1 to 3 mL, again with a maximum of 5 mg/kg of lidocaine, applied directly to open lacerations and wounds. It has a relatively fast onset (20 minutes) and its duration is 45 to 60 minutes. An advantage of this product is that it can be used on open skin, she said, adding, “this is our winner for lac repairs and debridements.” Also, the epinephrine component can help “stem bleeding if you’re doing a lac repair, so that’s a bonus.” One disadvantage of this product, however, is that the epinephrine “may cause vascular compromise,” said Dr. McKinney. “So you just want to be careful and watch out for that.”

For wounds that cover a very large surface area, she said, “sometimes it’s not practical to use those prepackaged products … you may exceed your maximum dose of lidocaine.” Another option for wounds that cover a large surface area is a “make your own” product known as “Lido-Lube.” A recipe she learned while a resident consists of 3 to 4 mg/kg of lidocaine (as 1% or 2% solution for injection) combined with surgical lubricant until it reaches the consistency of a thin gel. This product then can be applied generously to the wound.

Physostigmine Resurrected
For Anticholinergic Toxicity

Despite historical controversy, physostigmine can be used to treat anticholinergic toxicity, according to ED pharmacist Nicole M. Acquisto, PharmD, BCPS.

The controversy over the use of physostigmine “is rooted in a handful of case reports from the late 1970s to early 1980s,” said Dr. Acquisto. When used for anticholinergic toxicity, most often with tricyclic antidepressant [TCA] overdoses, it “was found to cause seizures and asystole,” she said. However, she added, the seizures were “most often due to a fast rate of administration or … other medications the patient ingested that cause seizure activity” and the asystole was “most often seen in patients with underlying cardiac arrhythmias or conduction disorders” (Ann Emerg Med 1980;9:588-590; Curr Opin Pediatr 2007;19:201-205).

Dr. Acquisto, an emergency medicine clinical pharmacy specialist and an assistant professor in the Department of Emergency Medicine at the University of Rochester Medical Center, in Rochester, N.Y., pointed to additional data supporting the effectiveness of ED pharmacy. A study of 52 patients, for example, showed that physostigmine worked better and faster than benzodiazepines for reversing agitation and delirium associated with anticholinergic toxicity due to pure anticholinergic agents, antihistamines, atypical antipsychotics and cyclic antidepressants (Ann Emerg Med 2000;374-381). She also pointed to a review of eight years of experience using physostigmine in this setting that showed a low rate of seizures (<1%) (Clin Toxicol 2010;48:648. Abstract 214.) and no cardiac arrhythmias and one 39-patient study during which one patient had a brief seizure (Ann Emerg Med 2003;42:14-19).

Dr. Acquisto noted that the ED staff at the University of Rochester Medical Center uses “physostigmine for patients with moderate to severe anticholinergic toxicity” to prevent patients from worsening to the point of needing intervention such as intubation, catheterization, or chemical or physical restraints. For adults, they use a dose of 0.5 to 2 mg, undiluted and given by IV push over 10 minutes, and in children, they use 0.01 to 0.03 mg/kg,also undiluted and given by IV push over 10 minutes. The onset is five to 10 minutes and the duration is 30 minutes to two hours, said Dr. Acquisto, noting that additional doses may be needed.

She said that they will even use it in patients who have anticholinergic toxicity related to TCA overdoses but not in patients who have contraindications, such as cardiac conduction abnormalities, bradycardia and gastrointestinal/urinary obstructions.

Propofol Makes Sense
For Alcohol Withdrawal

The neurobiochemistry of propofol makes it a useful option for treating patients with alcohol withdrawal, according to Darrel W. Hughes, PharmD, BCPS, a clinical specialist in emergency medicine at the University of Texas Health Science Center (UTHSC) at San Antonio.

Alcohol withdrawal “affects up to one-third of hospitalized patients, and it is associated with an increased mortality” of up to 300% in that population, said Dr. Hughes, referring to several studies (N Engl J Med 1995; 333:1058-1065; Crit Care Med 2010; 38[suppl]:s494-s501).

The criteria for diagnosing alcohol withdrawal include two or more of the following symptoms that develop hours to days after cessation or reduction of alcohol: autonomic hyperactivity, increased hand tremor, insomnia, nausea or vomiting, visual, tactile or auditory hallucinations or illusions, psychomotor agitation, anxiety and grand mal seizures.

Chronic ingestion of alcohol decreases γ-aminobutyric acid type A (GABA-A) receptor function and increases N-methyl-d-aspartate (NMDA) receptor function. When someone is drinking, alcohol acts as a GABA agonist, creating a balance between the two neurotransmitters, but during alcohol withdrawal, the decreased GABA activity results in tremors, diaphoresis, tachycardia, anxiety and seizures, and the NMDA overload results in delirium, hallucinations and seizures.

Benzodiazepines, which are commonly used to treat alcohol withdrawal, bind GABA-A, controlling agitation and reducing the duration of withdrawal symptoms, complications and mortality. But Dr. Hughes said that chronic use of benzodiazepines could lead to GABA-A receptor downregulation and refractoriness. “We do see patients who need really high doses because they often have downregulation of receptors.”

To address this problem, at UTHSC at San Antonio, once a patient is “determined to be refractory” to benzodiazepines, they try propofol, according to Dr. Hughes. At a dose of 5 to 80 mcg/kg per minute, propofol activates GABA-A receptors and inhibits the NMDA and glutamate receptor, better imitating the neurobiochemistry of alcohol. “It has been shown to be effective for benzodiazepine-resistant [alcohol] withdrawal,” he said. Additionally, propofol has a short half-life and predictable metabolism, which make “it an attractive medication.”

Dr. Hughes pointed out a few side effects to be aware of when using propofol in this setting: hypotension, hypertriglyceridemia and propofol-related infusion syndrome.

Intranasal Formulations Allow
Quick Delivery in the ED

New mucosal atomizers make it easier to administer medications intranasally, allowing for faster onset of effect for a variety of medications used in the emergency setting, according to a team from Chicago.

In her ED pearl presentation, Renee Petzel Gimbar, PharmD, a clinical pharmacist and clinical assistant professor at the University of Illinois Hospital and Health Sciences System, said that the hospital uses intranasal (IN) formulations of drugs including midazolam, fentanyl and naloxone for its emergency medical services (EMS) and in its ED.

Dr. Petzel Gimbar noted that mucosal atomizer devices deliver medication in a fine mist absorbed via the nasal mucosa. The maximum volume administered in each nostril is 1 mL, she noted, so it is important to use the highest medication concentration available to stay within that volume. “In adult patients, you are going to be limited by volume. You can only give that 2 mL total, so you may have to limit your use in overweight adult patients.”

For patients with pain conditions, such as fractures, burns and sickle cell crisis, IN delivery of fentanyl “can get them their medication very quickly” to provide pain relief. This was demonstrated in a study of patients aged 1 to 15 years who were given either IV morphine or IN fentanyl as determined by their physician. According to the researchers, fentanyl dosed at 1.5 mcg/kg decreased the time to administration by almost half compared with standard doses of morphine (32 minutes with fentanyl and 59 minutes with morphine) (Acad Emerg Med 2010;17:214-217).

This is “key,” said Dr. Petzel Gimbar. “You can give a dose in triage if, for example, you have a long bone fracture, to get them some pain relief almost immediately” before they even go for an x-ray. The benefit of this approach was shown in a prospective, nonblinded interventional study of 81 patients aged 3 to 18 years with clinically suspected fractures (Acad Emerg Med 2010;17:1155-1161). During the study, the patients were weighed in triage and given IN fentanyl (2 mcg/kg, maximum dose 100 mcg). The investigators measured pain scores at 10, 20 and 30 minutes. Dr. Petzel Gimbar noted that 72% of the patients had relief within 10 minutes, with 70% to 78% having a sustained decrease in pain relief over the study period. “Only 9% required a rescue analgesic after 20 minutes,” she said, adding that “no side effects were reported.”

Offering general dosing guidelines for fentanyl in this setting, Dr. Petzel Gimbar recommended 1 to 2 mcg/kg up to a maximum dose of 100 mcg, repeated once if no effect.

Fentanyl at that same dose, as well as midazolam, can be used to achieve moderate sedation in the ED, noted Dr. Petzel Gimbar. In pediatric patients with seizures/status epilepticus, studies comparing IN midazolam with rectal diazepam in the prehospital and ED settings showed that IN midazolam was “as effective, if not more effective” (J Child Neurol 2002;17:123-126; Pediatr Neurol2006;34:355-359; Pediatr Emerg Care 2007;23:148-153). For moderate sedation, she recommended an IN midazolam dose of 0.3 mg/kg up to a maximum of 10 mg, repeated once if no effect is seen.

For opioid toxicity, Dr. Petzel Gimbar pointed to a retrospective study of EMS patients comparing IN and IV naloxone (dose for both, 0.4 to 2 mg initially, up to a maximum of 10 mg), during which paramedics in the field found the IN formulation “to be as effective as IV naloxone” (Am J Emerg Med 2010;28:296-303). She further noted that IN naloxone can be used in the ED in patients without IV access, but she cautioned that it is important to obtain IV access in such patients as soon as possible.